In vivo degradation forms, anti-degradation strategies, and clinical applications of therapeutic peptides in non-infectious chronic diseases

Degradation of the α-Carboxyl Terminus 11 Peptide: In Vivo and Ex Vivo Impacts of Time, Temperature, Inhibitors, and Gender in Rat

“…PTases/PPTases are enzymes and their biological activities can be affected by multiple factors, such as temperature, time, substance concentration, pH, and antagonists or agonists. , In the present study, αCT11 degradation was highly time- and temperature-dependent in both male and female rats. The αCT11 concentration was reduced to 50% within 4–5 min in vivo and was almost undetectable at 10 min after tail vein injection (Figure ).…”

“…Figure C indicates that αCT11 quickly degraded in the blood circulation following the injection. At about 5 min postinjection, there was a ∼53% reduction of the initial αCT11 concentration, and the peptide was almost undetectable 10 min postinjection ( n = 3), implying that factors (e.g., proteases) in the plasma efficiently promoted αCT11 degradation …”

“…This study provides new insight into αCT11 degradation, and the findings may be used to prolong peptide half-life in the bloodstream, thus improving the efficiency of peptide-based therapy for patients with various diseases, such as cardiovascular disease. Moreover, while the issue of the instability of peptide therapeutics in vivo is generally known among those in the field and is well discussed in reviews of the literature, , there are few concrete examples of the phenomenon in the primary literature as illustrated in the present study.…”

“…Over the past decade, therapeutic peptides, 12,13 stem cells [e.g., embryonic stem cells, 14 induced pluripotential stem cells, fetal stem cells, adult stem cells 15 ], stem-cell-derived somatic cells [e.g., cardiomyocytes, 15 smooth muscle cells, 16,17 endothelial cells 15 ], stem cell transplantation in combination with biomaterials, 16,18−20 miRNAs, 21 gene therapy, 22 xenotransplantation of hearts, 23 and extracellular vesicles (EVs) 24 have been tested in preclinical studies and clinical trials. However, these treatments have yet to advance the standard of care for acute MI and subsequent HF due to multiple reasons, including limited options for treatment administration, the instability of novel therapeutics [such as peptides 25 and miRNAs in vivo 21 ], and uncertainties about the clinical efficacy of cellular therapies, such as stem cell engraftment. 17 Compared to stem cell and gene therapy, peptide-based treatments have shown promise for treating diseases, such as cardiovascular disorders, probably owing to their high affinity and specificity for their targets, as well as their relative safety and low number of side effects.…”

Discovering peptide inhibitors of thrombin as a strategy for anticoagulation

“…Additionally, the short peptides face big challenging for degradation in blood circulation, current techniques such as peptide N-or C-terminus modification, conjugating with macromolecule, or using drug delivery vehicle have shown promised effect for antidegradation. [33] Random peptide sequences were generated firstly, and the 3-D structures of the random 5-mer peptides were generated using Rosetta BuildPeptide. The 5-mer length random peptides have 5 20 possible compositions.…”